Elsevier

Experimental Eye Research

Volume 67, Issue 6, December 1998, Pages 637-645
Experimental Eye Research

Regular article
Increase in Interphotoreceptor Matrix Gelatinase A (MMP-2) Associated with Age-related Macular Degeneration

https://doi.org/10.1006/exer.1998.0552Get rights and content

Abstract

Matrix metalloproteinases have increasingly been shown to be associated with diseases involving neovascularization and/or abnormal cellular migration or proliferation. A number of diseases of this type affect the retina. In this study, the activity of gelatinase A (MMP-2), the most abundant matrix metalloproteinase in IPM (interphoto receptor matrix) and vitreous, was measured with respect to age in normal human donor eyes and compared to donors with age-related macular degeneration.

IPM and vitreous were obtained from a total of 88 human donors. Samples for electrophoresis were normalized for protein content and subjected to quantitative gelatin zymography. The zymograms were scanned and then digitized and quantitated using the NIH ‘Image’ program.

There was not a statistically significant change in the level of gelatinase A in IPM or vitreous as a function of age, although a slight downward trend was found in the total gelatinase A activity within the normal population. Likewise, when comparing normal and age-related macular degeneration donors, there was not a significant difference in the gelatinase A levels in vitreous or in retina-associated IPM. However, the level of gelatinase A was nearly doubled specifically in retinal pigment epithelium-associated IPM from eyes with age-related macular degeneration [0.99±0.09 U mg−1(56) vs  1.71±0.28 U mg−1(14) (mean±s.e.m.(number),P<0.0021; 1 unit=1.0 ng gelatin cleaved h−1). Gelatinase A may be associated with the changes that occur in age-related macular degeneration, especially the neovascularization which accompanies the exudative (‘wet’) form of the disease.

References (52)

  • D.E. Kleiner et al.

    Quantitative zymography: detection of picogram quantities of gelatinases

    Anal. Biochem.

    (1994)
  • D.S. Papermaster et al.

    Biosynthetic and immunochemical characterization of a large protein in frog and cattle rod outer segment membranes

    Exp. Eye Res.

    (1976)
  • J.J. Plantner

    A microassay for proteolytic activity

    Anal. Biochem.

    (1991)
  • J.J. Plantner et al.

    Polarized distribution of metalloproteinases in the bovine interphotoreceptor matrix

    Exp. Eye Res.

    (1994)
  • H. Sato et al.

    Activation of recombinant membrane type 1-matrix metalloproteinase (MT1-MMP) by furin and its interaction with tissue inhibitor of metalloproteinases (TIMP)-2

    FEBS Lett.

    (1996)
  • R.W. Young

    Pathophysiology of age-related macular degeneration

    Surv. Ophthalmol.

    (1987)
  • J.P. Alexander et al.

    Expression of matrix metalloproteinases and inhibitor by human retinal pigment epithelium

    Invest Ophthalmol. Vis. Sci.

    (1990)
  • R. Allikmets et al.

    Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration

    Science

    (1997)
  • H. Birkedal-Hansen et al.

    Matrix metalloproteinases: A review

    Crit. Rev. Oral Biol. Med.

    (1993)
  • D. Brown et al.

    Characterization of an endogenous metalloproteinase in human vitreous

    Curr. Eye Res.

    (1994)
  • P.A. Campochiaro et al.

    The extracellular matrix of human retinal pigment epithelial cells in vivo and its synthesis in vitro

    Invest. Ophthalmol. Vis. Sci.

    (1986)
  • M.R.C. Capon et al.

    Sorsby's fundus dystrophy. A light and electron microscopic study

    Ophthalmol.

    (1995)
  • K.A. Cingle et al.

    Age-related changes of glycosidases in human retinal pigment epithelium

    Curr. Eye Res.

    (1996)
  • M.D. Davis

    Proliferative diabetic retinopathy

    Retina

    (1994)
  • M.A. De La Paz et al.

    Exclusion of TIMP3 as a candidate locus in age-related macular degeneration

    Invest. Ophthalmol. Vis. Sci.

    (1997)
  • M.J. Elman et al.

    Exudative age-related macular degeneration

  • Cited by (0)

    Ryan, S. J

    f1

    Corresponding author: James J. Plantner, Center for Vision Research, Department of Ophthalmology, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106-5068, U.S.A.

    f2

    Current Address: Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, U.S.A.

    View full text